Gastrointestinal cancers continue to pose a significant global health challenge, with millions of new cases diagnosed each year. Despite advancements in treatment, the prognosis for many patients remains poor. This article explores the potential of garcinol, a polyisoprenylated benzophenone found in various Garcinia species, as a therapeutic agent against gastrointestinal malignancies. The objective is to review recent research on garcinol's anticancer properties, its mechanisms of action, and safety aspects. Garcinol exhibits anticancer effects in esophageal, gastric, colorectal, pancreatic, and liver cancers by inhibiting metastasis, inducing apoptosis, and targeting key molecular pathways in cancer progression. Nanotechnology is explored as a means to enhance garcinol delivery and efficacy. Safety assessments suggest a promising toxicity profile. Garcinol shows significant potential as a natural therapeutic agent for gastrointestinal cancers, and future research is needed on optimizing its delivery, exploring synergistic combinations, and conducting clinical trials to validate its efficacy and safety for clinical applications.

• Klíčová slova
• Apoptosis, Garcinol, Gastrointestinal cancers, Pharmacokinetics, Targeted therapy,
• MeSH
• antitumorózní látky fytogenní terapeutické užití   farmakologie   MeSH
• gastrointestinální nádory * prevence a kontrola   farmakoterapie   MeSH
• lidé MeSH
• terpeny * terapeutické užití   farmakologie   MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH
• Názvy látek
• antitumorózní látky fytogenní MeSH
• garcinol MeSH Prohlížeč
• terpeny * MeSH

Paclitaxel, a compound naturally occurring in yew, is a commonly used drug for the treatment of different types of cancer. Unfortunately, frequent cancer cell resistance significantly decreases its anticancer effectivity. The main reason for the resistance development is the paclitaxel-induced phenomenon of cytoprotective autophagy occurring by different mechanisms of action in dependence on a cell type and possibly even leading to metastases. Paclitaxel also induces autophagy in cancer stem cells, which greatly contributes to tumor resistance development. Paclitaxel anticancer effectivity can be predicted by the presence of several autophagy-related molecular markers, such as tumor necrosis factor superfamily member 13 in triple-negative breast cancer or cystine/glutamate transporter encoded by the SLC7A11 gene in ovarian cancer. Nevertheless, the undesired effects of paclitaxel-induced autophagy can be eliminated by paclitaxel co-administration with autophagy inhibitors, such as chloroquine. Interestingly, in certain cases, it is worthy of potentiating autophagy by paclitaxel combination with autophagy inducers, for instance, apatinib. A modern strategy in anticancer research is also to encapsulate chemotherapeutics into nanoparticle carriers or develop their novel derivatives with improved anticancer properties. Hence, in this review article, we summarize not only the current knowledge of paclitaxel-induced autophagy and its role in cancer resistance but mainly the possible drug combinations based on paclitaxel and their administration in nanoparticle-based formulations as well as paclitaxel analogs with autophagy-modulating properties.

• Klíčová slova
• Apoptosis, Autophagy markers, Cell death, Drug co-administration, Mitotic poisons, Nanoparticles, Taxol,
• MeSH
• antitumorózní látky fytogenní * farmakologie   terapeutické užití   MeSH
• apoptóza MeSH
• autofagie MeSH
• chemorezistence MeSH
• lidé MeSH
• nádorové buněčné linie MeSH
• nádory vaječníků * MeSH
• paclitaxel farmakologie   terapeutické užití   MeSH
• Check Tag
• lidé MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH
• Názvy látek
• antitumorózní látky fytogenní * MeSH
• paclitaxel MeSH

A set of fifteen triterpenoid pyrazines and pyridines was prepared from parent triterpenoid 3-oxoderivatives (betulonic acid, dihydrobetulonic acid, oleanonic acid, moronic acid, ursonic acid, heterobetulonic acid, and allobetulone). Cytotoxicity of all compounds was tested in eight cancer and two non-cancer cell lines. Evaluation of the structure-activity relationships revealed that the triterpenoid core determined whether the final molecule is active or not, while the heterocycle is able to increase the activity and modulate the specificity. Five compounds (1b, 1c, 2b, 2c, and 8) were found to be preferentially and highly cytotoxic (IC50 ≈ 1 μM) against leukemic cancer cell lines (CCRF-CEM, K562, CEM-DNR, or K562-TAX). Surprisingly, compounds 1c, 2b, and 2c are 10-fold more active in multidrug-resistant leukemia cells (CEM-DNR and K562-TAX) than in their non-resistant analogs (CCRF-CEM and K562). Pharmacological parameters were measured for the most promising candidates and two types of prodrugs were synthesized: 1) Sugar-containing conjugates, most of which had improved cell penetration and retained high cytotoxicity in the CCRF-CEM cell line, unfortunately, they lost the selectivity against resistant cells. 2) Medoxomil derivatives, among which compounds 26-28 gained activities of IC50 0.026-0.043 μM against K562 cells. Compounds 1b, 8, 21, 22, 23, and 24 were selected for the evaluation of the mechanism of action based on their highest cytotoxicity against CCRF-CEM cell line. Several experiments showed that the majority of them cause apoptosis via the mitochondrial pathway. Compounds 1b, 8, and 21 inhibit growth and disintegrate spheroid cultures of HCT116 and HeLa cells, which would be important for the treatment of solid tumors. In summary, compounds 1b, 1c, 2b, 2c, 24, and 26-28 are highly and selectively cytotoxic against cancer cell lines and were selected for future in vivo tests and further development of anticancer drugs.

• Klíčová slova
• Apoptosis, Cancer, Cytotoxicity, Electron microscopy, Fluorescence, Heterocycle, Huisgen cycloaddition, MDR, Medoxomil, Mitochondria, Molecular target, Pharmacology, Prodrug, Pyrazine, Pyridine, Spheroid cultures, Triterpene,
• MeSH
• antitumorózní látky fytogenní * farmakologie   MeSH
• antitumorózní látky * farmakologie   MeSH
• chemorezistence MeSH
• HeLa buňky MeSH
• lidé MeSH
• membránový potenciál mitochondrií MeSH
• nádorové buněčné linie MeSH
• prekurzory léčiv * farmakologie   MeSH
• pyraziny farmakologie   MeSH
• pyridiny farmakologie   MeSH
• triterpeny * farmakologie   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• antitumorózní látky fytogenní * MeSH
• antitumorózní látky * MeSH
• prekurzory léčiv * MeSH
• pyraziny MeSH
• pyridiny MeSH
• triterpeny * MeSH

The development of painful paclitaxel-induced peripheral neuropathy (PIPN) represents a major dose-limiting side effect of paclitaxel chemotherapy. Here we report a promising effect of duvelisib (Copiktra), a novel FDA-approved PI3Kδ/γ isoform-specific inhibitor, in preventing paclitaxel-induced pain-like behavior and pronociceptive signaling in DRGs and spinal cord dorsal horn (SCDH) in rat and mouse model of PIPN. Duvelisib blocked the development of mechanical hyperalgesia in both males and females. Moreover, duvelisib prevented paclitaxel-induced sensitization of TRPV1 receptors, and increased PI3K/Akt signaling in small-diameter DRG neurons and an increase of CD68+ cells within DRGs. Specific optogenetic stimulation of inhibitory neurons combined with patch-clamp recording revealed that duvelisib inhibited paclitaxel-induced weakening of inhibitory, mainly glycinergic control on SCDH excitatory neurons. Enhanced excitatory and reduced inhibitory neurotransmission in the SCDH following PIPN was also alleviated by duvelisib application. In summary, duvelisib showed a promising ability to prevent neuropathic pain in PIPN. The potential use of our findings in human medicine may be augmented by the fact that duvelisib is an FDA-approved drug with known side effects.SIGNIFICANCE STATEMENT We show that duvelisib, a novel FDA-approved PI3Kδ/γ isoform-specific inhibitor, prevents the development of paclitaxel-induced pain-like behavior in males and females and prevents pronociceptive signaling in DRGs and spinal cord dorsal horn in rat and mouse model of paclitaxel-induced peripheral neuropathy.

• Klíčová slova
• PI3K, TRPV1, dorsal horn, glycine, neuropathy, pain,
• MeSH
• antitumorózní látky fytogenní * farmakologie   MeSH
• bolest MeSH
• fosfatidylinositol-3-kinasy MeSH
• hyperalgezie chemicky indukované   farmakoterapie   prevence a kontrola   MeSH
• isochinoliny MeSH
• krysa rodu Rattus MeSH
• myši MeSH
• nemoci periferního nervového systému MeSH
• neuralgie * chemicky indukované   farmakoterapie   prevence a kontrola   MeSH
• paclitaxel škodlivé účinky   MeSH
• puriny MeSH
• zvířata MeSH
• Check Tag
• krysa rodu Rattus MeSH
• mužské pohlaví MeSH
• myši MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• antitumorózní látky fytogenní * MeSH
• duvelisib MeSH Prohlížeč
• isochinoliny MeSH
• paclitaxel MeSH
• puriny MeSH

This review focuses on the specific biological effects of optically pure silymarin flavo-nolignans, mainly silybins A and B, isosilybins A and B, silychristins A and B, and their 2,3-dehydro derivatives. The chirality of these flavonolignans is also discussed in terms of their analysis, preparative separation and chemical reactions. We demonstrated the specific activities of the respective diastereomers of flavonolignans and also the enantiomers of their 2,3-dehydro derivatives in the 3D anisotropic systems typically represented by biological systems. In vivo, silymarin flavonolignans do not act as redox antioxidants, but they play a role as specific ligands of biological targets, according to the "lock-and-key" concept. Estrogenic, antidiabetic, anticancer, antiviral, and antiparasitic effects have been demonstrated in optically pure flavonolignans. Potential application of pure flavonolignans has also been shown in cardiovascular and neurological diseases. Inhibition of drug-metabolizing enzymes and modulation of multidrug resistance activity by these compounds are discussed in detail. The future of "silymarin applications" lies in the use of optically pure components that can be applied directly or used as valuable lead structures, and in the exploration of their true molecular effects.

• Klíčová slova
• Silybum marianum, chirality, dehydroflavonolignan, diastereomer, flavonoid, flavonolignan, isosilybin, milk thistle, silibinin, silybin, silychristin, silydianin, silymarin,
• MeSH
• antiinfekční látky chemie   farmakologie   MeSH
• antioxidancia chemie   farmakologie   MeSH
• antitumorózní látky fytogenní chemie   farmakologie   MeSH
• lidé MeSH
• silibinin chemie   farmakologie   MeSH
• stereoizomerie MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH
• Názvy látek
• antiinfekční látky MeSH
• antioxidancia MeSH
• antitumorózní látky fytogenní MeSH
• silibinin MeSH

Pancracine, a montanine-type Amaryllidaceae alkaloid (AA), is one of the most potent compounds among natural isoquinolines. In previous studies, pancracine exhibited cytotoxic activity against diverse human cancer cell lines in vitro. However, further insight into the molecular mechanisms that underlie the cytotoxic effect of pancracine have not been reported and remain unknown. To fill this void, the cell proliferation and viability of cancer cells was explored using the Trypan Blue assay or by using the xCELLigence system. The impact on the cell cycle was determined by flow cytometry. Apoptosis was evaluated by Annexin V/PI and by quantifying the activity of caspases (-3/7, -8, and -9). Proteins triggering growth arrest or apoptosis were detected by Western blotting. Pancracine has strong antiproliferative activity on A549 cells, lasting up to 96 h, and antiproliferative and cytotoxic effects on MOLT-4 cells. The apoptosis-inducing activity of pancracine in MOLT-4 cells was evidenced by the significantly higher activity of caspases. This was transmitted through the upregulation of p53 phosphorylated on Ser392, p38 MAPK phosphorylated on Thr180/Tyr182, and upregulation of p27. The pancracine treatment negatively altered the proliferation of A549 cells as a consequence of an increase in G1-phase accumulation, associated with the downregulation of Rb phosphorylated on Ser807/811 and with the concomitant upregulation of p27 and downregulation of Akt phosphorylated on Thr308. This was the first study to glean a deeper mechanistic understanding of pancracine activity in vitro. Perturbation of the cell cycle and induction of apoptotic cell death were considered key mechanisms of pancracine action.

• Klíčová slova
• Amaryllidaceae alkaloids, antiproliferative activity, apoptosis, cell cycle arrest, cytotoxicity, pancracine,
• MeSH
• adenokarcinom plic patologie   MeSH
• alkaloidy izolace a purifikace   farmakologie   MeSH
• Amaryllidaceae chemie   MeSH
• antitumorózní látky fytogenní izolace a purifikace   farmakologie   MeSH
• apoptóza účinky léků   MeSH
• buňky A549 MeSH
• buňky Hep G2 MeSH
• heterocyklické sloučeniny tetra- a více cyklické izolace a purifikace   farmakologie   MeSH
• leukemie patologie   MeSH
• lidé MeSH
• MFC-7 buňky MeSH
• nádorové buněčné linie MeSH
• nádory plic patologie   MeSH
• proliferace buněk účinky léků   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• alkaloidy MeSH
• antitumorózní látky fytogenní MeSH
• heterocyklické sloučeniny tetra- a více cyklické MeSH
• pancracine MeSH Prohlížeč

Prenylated or geranylated flavonoids have been studied for their promising antiproliferative and cytotoxic activities. Twelve natural geranylated flavonoids (1-12) were isolated from the fruit of Paulownia tomentosa Steud. Their structures were elucidated using UV and IR spectroscopy, mass spectrometry, and 1D and 2D NMR spectroscopy. The absolute configurations were determined using NMR and circular dichroism. Seven of the compounds were characterized as new geranylated derivatives isolated from a natural source for the first time, namely 3'-O-methyl-5'-hydroxyisodiplacone (3), paulodiplacone A (5), tomentone II (6), tomentone B (7), tomentodiplacone P (8), paulodiplacone B (9), and tomentoflavone A (12). After 24 h of incubation at concentrations in the range 1-30 μM, the isolated compounds were tested for their antiproliferative and cytotoxic potentials against the human monocytic leukaemia cell line THP-1, using WST-1 and LDH assays, respectively. Almost all of the test compounds induced a concentration-dependent reduction in the metabolic activity of THP-1 cells and a concentration-dependent reduction in the cell viability. Diplacone (1) was the most potent antiproliferative and cytotoxic agent (IC50 9.31 ± 0.72 μM, LC50 18.01 ± 1.19 µM). 3'-O-Methyl-5'-hydroxydiplacone (2) showed relatively strong antiproliferative effect (IC50 12.61 ± 0.90 μM) and weaker cytotoxic activity (LC50 > 30 μM), indicating that it may serve as a potential lead compound for further testing. The structure-activity relationship for the 12 isolated compounds is discussed.

• Klíčová slova
• Antiproliferative activity, Cytotoxic activity, Flavonoid, Geranyl, Paulownia tomentosa, Prenyl, THP-1 cell line,
• MeSH
• antitumorózní látky fytogenní chemie   izolace a purifikace   farmakologie   MeSH
• flavonoidy chemie   izolace a purifikace   farmakologie   MeSH
• léky antitumorózní - screeningové testy MeSH
• lidé MeSH
• Magnoliopsida chemie   MeSH
• molekulární struktura MeSH
• nádorové buňky kultivované MeSH
• ovoce chemie   MeSH
• proliferace buněk účinky léků   MeSH
• rostlinné extrakty chemie   izolace a purifikace   farmakologie   MeSH
• viabilita buněk účinky léků   MeSH
• vztah mezi dávkou a účinkem léčiva MeSH
• vztahy mezi strukturou a aktivitou MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• antitumorózní látky fytogenní MeSH
• flavonoidy MeSH
• rostlinné extrakty MeSH

The aim of the study was to broadly determine the biological activities of purple potato ethanolic extract of the Blue Congo variety (BCE). The antioxidant activity of BCE was determined in relation to liposome membranes, and peroxidation was induced by UVB and AAPH. To clarify the antioxidant activity of BCE, we investigated its interactions with hydrophilic and hydrophobic regions of a membrane using fluorimetric and FTIR methods. Next, we investigated the cytotoxicity and pro-apoptotic activities of BCE in two human colon cancer cell lines (HT-29 and Caco-2) and in normal cells (IPEC-J2). In addition, the ability to inhibit enzymes that are involved in pro-inflammatory reactions was examined. Furthermore, BCE interactions with serum albumin and plasmid DNA were investigated using steady state fluorescence spectroscopy and a single molecule fluorescence technique (TCSPC-FCS). We proved that BCE effectively protects lipid membranes against the process of peroxidation and successfully inhibits the cyclooxygenase and lipoxygenase enzymes. Furthermore, it interacts with the hydrophilic and hydrophobic parts of lipid membranes as well as with albumin and plasmid DNA. It was observed that BCE is more cytotoxic against colon cancer cell lines than normal IPEC-J2 cells; it also induces apoptosis in cancer cell lines, but does not induce cell death in normal cells.

• MeSH
• albuminy MeSH
• antioxidancia chemie   farmakologie   MeSH
• antitumorózní látky fytogenní chemie   farmakologie   MeSH
• inhibitory cyklooxygenasy chemie   farmakologie   MeSH
• inhibitory lipoxygenas chemie   farmakologie   MeSH
• lidé MeSH
• lipidy chemie   MeSH
• liposomy MeSH
• nádorové buněčné linie MeSH
• plazmidy MeSH
• reaktivní formy kyslíku MeSH
• rostlinné extrakty chemie   farmakologie   MeSH
• sérový albumin chemie   metabolismus   MeSH
• Solanum tuberosum chemie   MeSH
• vazba proteinů MeSH
• viabilita buněk účinky léků   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• albuminy MeSH
• antioxidancia MeSH
• antitumorózní látky fytogenní MeSH
• inhibitory cyklooxygenasy MeSH
• inhibitory lipoxygenas MeSH
• lipidy MeSH
• liposomy MeSH
• reaktivní formy kyslíku MeSH
• rostlinné extrakty MeSH
• sérový albumin MeSH

BACKGROUND: Curcumin is an ingredient in the turmeric plant that gives yellow color to dishes and is used as a spice. It has been used locally/topically and systemically in the treatment of diseases in Far Eastern societies, especially in Indian and Chinese traditional medicine. Curcumin is a natural substance that does not show toxic properties in overdose. In addition to its anti-inflammatory, anti-oxidant, anti-neoplastic, anti-viral, anti-microbial, anti-angiogenic properties, platelet aggregation, apoptosis, and wound healing have been demonstrated in different studies. In recent years, it has been used as a radiosensitizing agent and a radioprotector in radiation therapy. Although curcumin has low bio-availability, it seems to be the ideal molecule due to its low molecular weight, high activity in inhibiting the growth of tumor cells and protecting normal tissues from the side effects of radiation. PURPOSE: Curcumin in combination with radiotherapy was discussed in the light of the literature.

• Klíčová slova
• curcumin, radiosensitizing agent– radioprotector, radiotherapy,
• MeSH
• antitumorózní látky fytogenní farmakologie   MeSH
• kurkumin farmakologie   MeSH
• lidé MeSH
• nádory * farmakoterapie   radioterapie   MeSH
• radioprotektivní látky farmakologie   MeSH
• radiosenzibilizující látky farmakologie   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• antitumorózní látky fytogenní MeSH
• kurkumin MeSH
• radioprotektivní látky MeSH
• radiosenzibilizující látky MeSH

Comprehensive scientific data provide evidence that isolated phytochemicals or whole plant foods may beneficially modify carcinogenesis. The aim of this study was to evaluate the oncostatic activities of Rhus coriaria L. (sumac) using animal models (rat and mouse), and cell lines of breast carcinoma. R. coriaria (as a powder) was administered through the diet at two concentrations (low dose: 0.1% (w/w) and high dose: 1 % (w/w)) for the duration of the experiment in a syngeneic 4T1 mouse and chemically-induced rat mammary carcinoma models. After autopsy, histopathological and molecular analyses of tumor samples in rodents were performed. Moreover, in vitro analyses using MCF-7 and MDA-MB-231 cells were conducted. The dominant metabolites present in tested R. coriaria methanolic extract were glycosides of gallic acid (possible gallotannins). In the mouse model, R. coriaria at a higher dose (1%) significantly decreased tumor volume by 27% when compared to controls. In addition, treated tumors showed significant dose-dependent decrease in mitotic activity index by 36.5% and 51% in comparison with the control group. In the chemoprevention study using rats, R. coriaria at a higher dose significantly reduced the tumor incidence by 20% and in lower dose non-significantly reduced tumor frequency by 29% when compared to controls. Evaluations of the mechanism of oncostatic action using valid clinical markers demonstrated several positive alterations in rat tumor cells after the treatment with R. coriaria. In this regard, histopathological analysis of treated tumor specimens showed robust dose-dependent decrease in the ratio of high-/low-grade carcinomas by 66% and 73% compared to controls. In treated rat carcinomas, we found significant caspase-3, Bax, and Bax/Bcl-2 expression increases; on the other side, a significant down-regulation of Bcl-2, Ki67, CD24, ALDH1, and EpCam expressions and MDA levels. When compared to control specimens, evaluation of epigenetic alterations in rat tumor cells in vivo showed significant dose-dependent decrease in lysine methylation status of H3K4m3 and H3K9m3 and dose-dependent increase in lysine acetylation in H4K16ac levels (H4K20m3 was not changed) in treated groups. However, only in lower dose of sumac were significant decreases in the expression of oncogenic miR210 and increase of tumor-suppressive miR145 (miR21, miR22, and miR155 were not changed) observed. Finally, only in lower sumac dose, significant decreases in methylation status of three out of five gene promoters-ATM, PTEN, and TIMP3 (PITX2 and RASSF1 promoters were not changed). In vitro evaluations using methanolic extract of R. coriaria showed significant anticancer efficacy in MCF-7 and MDA-MB-231 cells (using Resazurin, cell cycle, annexin V/PI, caspase-3/7, Bcl-2, PARP, and mitochondrial membrane potential analyses). In conclusion, sumac demonstrated significant oncostatic activities in rodent models of breast carcinoma that were validated by mechanistic studies in vivo and in vitro.

• Klíčová slova
• MCF-7 cells, MDA-MB-231 cells, Rhus coriaria, angiogenesis, apoptosis, breast cancer, cancer stem cells, cell proliferation, epigenetics, mouse, rat, sumac,
• MeSH
• antitumorózní látky fytogenní farmakologie   MeSH
• apoptóza MeSH
• buněčný cyklus MeSH
• lidé MeSH
• mikro RNA genetika   MeSH
• myši inbrední BALB C MeSH
• myši nahé MeSH
• myši MeSH
• nádorové biomarkery genetika   metabolismus   MeSH
• nádorové buňky kultivované MeSH
• nádory prsu farmakoterapie   metabolismus   patologie   MeSH
• potkani Sprague-Dawley MeSH
• proliferace buněk MeSH
• regulace genové exprese u nádorů účinky léků   MeSH
• Rhus chemie   MeSH
• rostlinné extrakty farmakologie   MeSH
• xenogenní modely - testy antitumorózní aktivity MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• myši MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• antitumorózní látky fytogenní MeSH
• mikro RNA MeSH
• nádorové biomarkery MeSH
• rostlinné extrakty MeSH